Antisense compounds have been shown to be effective for modulating the amount, activity, and/or function of cellular target nucleic acids. Certain chemical modifications have been incorporated into antisense oligonucleotides to enhance one or more properties of such antisense compounds. In certain instances, such chemically modified oligonucleotides have been shown to possess desirable characteristics compared to unmodified oligonucleotides, such as improved affinity for target and/or resistance to degradation. Chemically modified antisense oligonucleotides have been shown to have value as research tools, diagnostic reagents, and therapeutic agents, depending on the target nucleic acid and chemical modifications.
Certain nucleic acid molecules have been shown to localize to cellular sub-organelles. Certain such nucleic acid molecules are RNA molecules, including non-coding RNA molecules. For example, small nucleolar RNA molecules (snoRNA) localize to the nucleolus inside the nucleus of eukaryotic cells. In certain instances, such snoRNA have been shown to be associated with precursors of ribosomal RNA (rRNA). Accordingly, certain snoRNAs have been reported to be involved in nucleotide modification and processing of pre-rRNA. Nucleic acids have also been found in Cajal bodies within the nucleus. RNA found in Cajal bodies have been referred to as small Cajal body-specific RNA (scaRNA). Certain scaRNA have been reported to be involved in nucleotide modification of spliceosomal small nuclear RNAs (snRNAs).
Certain ncRNAs, including miRNAs and snoRNAs, are involved in biological processes, such as DNA and RNA production, and translation. However, functionalizing individual ncRNAs has lagged in time, mainly due to lack of convenient knockout or knockdown approaches in mammals. This is especially the case for ncRNAs that localize to cellular sub-organelles, such as snoRNAs and scaRNAs.